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1.
Emerg Infect Dis ; 28(4): 743-750, 2022 04.
Article in English | MEDLINE | ID: covidwho-1770999

ABSTRACT

Patients undergoing chronic hemodialysis were among the first to receive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations because of their increased risk for severe coronavirus disease and high case-fatality rates. By using a previously reported cohort from Germany of at-risk hemodialysis patients and healthy donors, where antibody responses were examined 3 weeks after the second vaccination, we assessed systemic cellular and humoral immune responses in serum and saliva 4 months after vaccination with the Pfizer-BioNTech BNT162b2 vaccine using an interferon-γ release assay and multiplex-based IgG measurements. We further compared neutralization capacity of vaccination-induced IgG against 4 SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, and Delta) by angiotensin-converting enzyme 2 receptor-binding domain competition assay. Sixteen weeks after second vaccination, compared with 3 weeks after, cellular and humoral responses against the original SARS-CoV-2 isolate and variants of concern were substantially reduced. Some dialysis patients even had no detectable B- or T-cell responses.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines , Humans , Immunity, Humoral , RNA, Messenger , Renal Dialysis , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Vaccination
2.
Front Immunol ; 13: 828053, 2022.
Article in English | MEDLINE | ID: covidwho-1731780

ABSTRACT

Recent increases in SARS-CoV-2 infections have led to questions about duration and quality of vaccine-induced immune protection. While numerous studies have been published on immune responses triggered by vaccination, these often focus on studying the impact of one or two immunisation schemes within subpopulations such as immunocompromised individuals or healthcare workers. To provide information on the duration and quality of vaccine-induced immune responses against SARS-CoV-2, we analyzed antibody titres against various SARS-CoV-2 antigens and ACE2 binding inhibition against SARS-CoV-2 wild-type and variants of concern in samples from a large German population-based seroprevalence study (MuSPAD) who had received all currently available immunisation schemes. We found that homologous mRNA-based or heterologous prime-boost vaccination produced significantly higher antibody responses than vector-based homologous vaccination. Ad26.CoV2S.2 performance was particularly concerning with reduced titres and 91.7% of samples classified as non-responsive for ACE2 binding inhibition, suggesting that recipients require a booster mRNA vaccination. While mRNA vaccination induced a higher ratio of RBD- and S1-targeting antibodies, vector-based vaccines resulted in an increased proportion of S2-targeting antibodies. Given the role of RBD- and S1-specific antibodies in neutralizing SARS-CoV-2, their relative over-representation after mRNA vaccination may explain why these vaccines have increased efficacy compared to vector-based formulations. Previously infected individuals had a robust immune response once vaccinated, regardless of which vaccine they received, which could aid future dose allocation should shortages arise for certain manufacturers. Overall, both titres and ACE2 binding inhibition peaked approximately 28 days post-second vaccination and then decreased.


Subject(s)
/immunology , COVID-19/immunology , Immunity, Humoral/immunology , SARS-CoV-2/growth & development , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antibody Formation/immunology , Cross-Sectional Studies , Germany , Humans , Seroepidemiologic Studies , Spike Glycoprotein, Coronavirus/immunology , Vaccination/methods
3.
BMC Med ; 20(1): 102, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1724486

ABSTRACT

BACKGROUND: The COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, the Omicron variant was discovered and immediately classified as a variant of concern (VOC), since it shows substantially more mutations in the spike protein than any previous variant, especially in the receptor-binding domain (RBD). We analyzed the binding of the Omicron RBD to the human angiotensin-converting enzyme-2 receptor (ACE2) and the ability of human sera from COVID-19 patients or vaccinees in comparison to Wuhan, Beta, or Delta RBD variants. METHODS: All RBDs were produced in insect cells. RBD binding to ACE2 was analyzed by ELISA and microscale thermophoresis (MST). Similarly, sera from 27 COVID-19 patients, 81 vaccinated individuals, and 34 booster recipients were titrated by ELISA on RBDs from the original Wuhan strain, Beta, Delta, and Omicron VOCs. In addition, the neutralization efficacy of authentic SARS-CoV-2 wild type (D614G), Delta, and Omicron by sera from 2× or 3× BNT162b2-vaccinated persons was analyzed. RESULTS: Surprisingly, the Omicron RBD showed a somewhat weaker binding to ACE2 compared to Beta and Delta, arguing that improved ACE2 binding is not a likely driver of Omicron evolution. Serum antibody titers were significantly lower against Omicron RBD compared to the original Wuhan strain. A 2.6× reduction in Omicron RBD binding was observed for serum of 2× BNT162b2-vaccinated persons. Neutralization of Omicron SARS-CoV-2 was completely diminished in our setup. CONCLUSION: These results indicate an immune escape focused on neutralizing antibodies. Nevertheless, a boost vaccination increased the level of anti-RBD antibodies against Omicron, and neutralization of authentic Omicron SARS-CoV-2 was at least partially restored. This study adds evidence that current vaccination protocols may be less efficient against the Omicron variant.


Subject(s)
COVID-19 , COVID-19/prevention & control , Humans , Pandemics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
4.
Dtsch Arztebl Int ; 118(48): 824-831, 2021 12 03.
Article in English | MEDLINE | ID: covidwho-1706269

ABSTRACT

BACKGROUND: Until now, information on the spread of SARS-CoV-2 infections in Germany has been based mainly on data from the public health offices. It may be assumed that these data do not include many cases of asymptomatic and mild infection. METHODS: We determined seroprevalence over the course of the pandemic in a sequential, multilocal seroprevalence study (MuSPAD). Study participants were recruited at random in seven administrative districts (Kreise) in Germany from July 2020 onward; each participant was tested at two different times 3-5 months apart. Test findings on blood samples were used to determine the missed-case rate of reported infections, the infection fatality rate (IFR), and the association between seropositivity and demographic, socio-economic, and health-related factors, as well as to evaluate the self-reported results of PCR and antigenic tests. The registration number of this study is DRKS00022335. RESULTS: Among non-vaccinated persons, the seroprevalence from July to December 2020 was 1.3-2.8% and rose between February and May 2021 to 4.1-13.1%. In July 2021, 35% of tested persons in Chemnitz were not vaccinated, and the seroprevalence among these persons was 32.4% (07/2021). The surveillance detection ratio (SDR), i.e., the ratio between the true number of infections estimated from seroprevalence and the actual number or reported infections, varied among the districts included in the study from 2.2 to 5.1 up to December 2020 and from 1.3 to 2.9 up to June 2021, and subsequently declined. The IFR was in the range of 0.8% to 2.4% in all regions except Magdeburg, where a value of 0.3% was calculated for November 2020. A lower educational level was associated with a higher seropositivity rate, smoking with a lower seropositivity rate. On average, 1 person was infected for every 8.5 persons in quarantine. CONCLUSION: Seroprevalence was low after the first wave of the pandemic but rose markedly during the second and third waves. The missed-case rate trended downward over the course of the pandemic.


Subject(s)
COVID-19 , SARS-CoV-2 , Germany/epidemiology , Humans , Pandemics , Seroepidemiologic Studies
5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-317842

ABSTRACT

The SARS-CoV-2 pandemic calls for the rapid development of diagnostic, preventive, and therapeutic approaches. CD4 + and CD8 + T cell-mediated immunity is central for control of and protection from viral infections [1-3] . A prerequisite to characterize T-cell immunity, but also for the development of vaccines and immunotherapies, is the identification of the exact viral T-cell epitopes presented on human leukocyte antigens (HLA) [2-8] . This is the first work identifying and characterizing SARS-CoV-2-specific and cross-reactive HLA class I and HLA-DR T-cell epitopes in SARS-CoV-2 convalescents (n = 180) as well as unexposed individuals (n = 185) and confirming their relevance for immunity and COVID-19 disease course. SARS-CoV-2-specific T-cell epitopes enabled detection of post-infectious T-cell immunity, even in seronegative convalescents. Cross-reactive SARS-CoV-2 T-cell epitopes revealed preexisting T-cell responses in 81% of unexposed individuals, and validation of similarity to common cold human coronaviruses provided a functional basis for postulated heterologous immunity [9] in SARS-CoV-2 infection [10,11] . Intensity of T-cell responses and recognition rate of T-cell epitopes was significantly higher in the convalescent donors compared to unexposed individuals, suggesting that not only expansion, but also diversity spread of SARS-CoV-2 T-cell responses occur upon active infection. Whereas anti-SARS-CoV-2 antibody levels were associated with severity of symptoms in our SARS-CoV-2 donors, intensity of T-cell responses did not negatively affect COVID-19 severity. Rather, diversity of SARS-CoV-2 T-cell responses was increased in case of mild symptoms of COVID-19, providing evidence that development of immunity requires recognition of multiple SARS-CoV-2 epitopes. Together, the specific and cross-reactive SARS-CoV-2 T-cell epitopes identified in this work enable the identification of heterologous and post-infectious T-cell immunity and facilitate the development of diagnostic, preventive, and therapeutic measures for COVID-19.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296970

ABSTRACT

Background: The ongoing COVID-19 pandemic is caused by the beta coronavirus SARS-CoV-2. COVID-19 manifests itself from mild or even asymptomatic infections to severe forms of life-threatening pneumonia. At the end of November 2021, yet another novel SARS-CoV-2 variant named B.1.1.529 or Omicron was discovered and classified as a variant of concern (VoC) by the WHO. Omicron shows significantly more mutations in the amino acid (aa) sequence of its spike protein than any previous variant, with the majority of those concentrated in the receptor binding domain (RBD). In this work, the binding of the Omicron RBD to the human ACE2 receptor was experimentally analyzed in comparison to the original Wuhan SARS-CoV-2 virus, and the Beta and Delta variants. Moreover, we compared the ability of human sera from COVID-19 convalescent donors and persons fully vaccinated with BNT162b2 (Corminaty) or Ad26.COV2.S (Janssen COVID-19 vaccine) as well as individuals who had boost vaccine doses with BNT162b2 or mRNA-1273 (Spikevax) to bind the different RBDs variants. Methods The Omicron RBD with 15 aa mutations compared to the original Wuhan strain was produced baculovirus-free in insect cells. Binding of the produced Omicron RBD to hACE was analyzed by ELISA. Sera from 27 COVID-19 patients, of whom 21 were fully vaccinated and 16 booster recipients were titrated on the original Wuhan strain, Beta, Delta and Omicron RBD and compared to the first WHO International Standard for anti-SARS-CoV-2 immunoglobulin (human) using the original Wuhan strain as reference. Results The Omicron RBD showed a slightly reduced binding to ACE2 compared to the other RBDs. The serum of COVID-19 patients, BNT162b2 vaccinated and boost vaccinated persons showed a reduced binding to Omicron RBD in comparison to the original Wuhan strain, Beta und Delta RBDs. In this assay, the boost vaccination did not improve the RBD binding when compared to the BNT162b2 fully vaccinated group. The RBD binding of the Ad26.COV2.S serum group was lower at all compared to the other groups. Conclusions The reduced binding of human sera to Omicron RBD provides first hints that the current vaccinations using BNT162b2, mRNA-1273 and Ad26.COV2.S may be less efficient in preventing infections with the Omicron variant.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294629

ABSTRACT

Background: While SARS-CoV-2 vaccinations were successful in decreasing COVID-19 caseloads, recent increases in SARS-CoV-2 infections have led to questions about duration and quality of the subsequent immune response. While numerous studies have been published on immune responses triggered by vaccination, these often focused on the initial peak response generated in specific population subgroups (e.g. healthcare workers or immunocompromised individuals) and have often only examined the effects of one or two different immunisation schemes. Methods and Findings We analysed serum samples from participants of a large German seroprevalence study (MuSPAD) who had received all available vaccines and dose schedules (mRNA-1273, BNT162b2, AZD1222, Ad26.CoV2S.2 or a combination of AZD1222 plus either mRNA-1273 or BNT162b2). Antibody titers against various SARS-CoV-2 antigens and ACE2 binding inhibition against SARS-CoV-2 wild-type and the Alpha, Beta, Gamma and Delta variants of concern were analysed using a previously published multiplex immunoassay MULTICOV-AB and an ACE2-RBD competition assay. Among the different vaccines and their dosing regimens, homologous mRNA-based or heterologous prime-boost vaccination produced significantly higher antibody responses than vector-based homologous vaccination. Ad26.CoV2S.2 performance was significantly reduced, even compared to AZD1222, with 91.67% of samples being considered non-responsive forACE2 binding inhibition. mRNA-based vaccination induced a higher ratio of RBD- and S1-targeting antibodies than vector-based vaccination, which resulted in an increased proportion of S2-targeting antibodies. Previously infected individuals had a robust immune response once vaccinated, regardless of which vaccine they received. When examining antibody kinetics post-vaccination after homologous immunisation regimens, both titers and ACE2 binding inhibition peaked approximately 28 days post-vaccination and then decreased as time increased. Conclusions As one of the first and largest population-based studies to examine vaccine responses for all currently available immunisation schemes in Germany, we found that homologous mRNA or heterologous vaccination elicited the highest immune responses. The high percentage of non-responders for Ad26.CoV2.S requires further investigation and suggests that a booster dose with an mRNA-based vaccine may be necessary. The high responses seen in recovered and vaccinated individuals could aid future dose allocation, should shortages arise for certain manufacturers. Given the role of RBD- and S1-specific antibodies in neutralising SARS-CoV-2, their relative over-representation after mRNA vaccination may explain why mRNA vaccines have an increased efficacy compared to vector-based formulations. Further investigation on these differences will be of particular interest for vaccine development and efficacy, especially for the next-generation of vector-based vaccines.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293501

ABSTRACT

Background: While SARS-CoV-2 vaccinations were successful in decreasing COVID-19 caseloads, recent increases in SARS-CoV-2 infections have led to questions about duration and quality of the subsequent immune response. While numerous studies have been published on immune responses triggered by vaccination, these often focused on the initial peak response generated in specific population subgroups (e.g. healthcare workers or immunocompromised individuals) and have often only examined the effects of one or two different immunisation schemes. Methods and Findings We analysed serum samples from participants of a large German seroprevalence study (MuSPAD) who had received all available vaccines and dose schedules (mRNA-1273, BNT162b2, AZD1222, Ad26.CoV2S.2 or a combination of AZD1222 plus either mRNA-1273 or BNT162b2). Antibody titers against various SARS-CoV-2 antigens and ACE2 binding inhibition against SARS-CoV-2 wild-type and the Alpha, Beta, Gamma and Delta variants of concern were analysed using a previously published multiplex immunoassay MULTICOV-AB and an ACE2-RBD competition assay. Among the different vaccines and their dosing regimens, homologous mRNA-based or heterologous prime-boost vaccination produced significantly higher antibody responses than vector-based homologous vaccination. Ad26.CoV2S.2 performance was significantly reduced, even compared to AZD1222, with 91.67% of samples being considered non-responsive forACE2 binding inhibition. mRNA-based vaccination induced a higher ratio of RBD- and S1-targeting antibodies than vector-based vaccination, which resulted in an increased proportion of S2-targeting antibodies. Previously infected individuals had a robust immune response once vaccinated, regardless of which vaccine they received. When examining antibody kinetics post-vaccination after homologous immunisation regimens, both titers and ACE2 binding inhibition peaked approximately 28 days post-vaccination and then decreased as time increased. Conclusions As one of the first and largest population-based studies to examine vaccine responses for all currently available immunisation schemes in Germany, we found that homologous mRNA or heterologous vaccination elicited the highest immune responses. The high percentage of non-responders for Ad26.CoV2.S requires further investigation and suggests that a booster dose with an mRNA-based vaccine may be necessary. The high responses seen in recovered and vaccinated individuals could aid future dose allocation, should shortages arise for certain manufacturers. Given the role of RBD- and S1-specific antibodies in neutralising SARS-CoV-2, their relative over-representation after mRNA vaccination may explain why mRNA vaccines have an increased efficacy compared to vector-based formulations. Further investigation on these differences will be of particular interest for vaccine development and efficacy, especially for the next-generation of vector-based vaccines.

9.
Vaccines (Basel) ; 9(10)2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1444355

ABSTRACT

To provide initial data on local SARS-CoV-2 epidemiology and spread in indigenous communities in north-eastern Colombia, respiratory swabs and serum samples from volunteers of indigenous communities were examined in March and April 2021. Samples from non-indigenous Colombians from the same villages were included as well. While previous exposure to SARS-CoV-2 was assessed by analysing serum samples for IgG and IgM with a rapid antibody point-of-care-test (POCT), screening for active infections was carried out with an antigen POCT test and real-time PCR from nasal swabs. In 380 indigenous and 72 non-indigenous volunteers, 61 (13.5%) active infections and an additional 113 (25%) previous infections were identified using diagnostic serology and molecular assays. Previous infections were more frequent in non-indigenous volunteers, and relevant associations of clinical features with active or previous SARS-CoV-2 infections were not observed. Symptoms reported were mild to moderate. SARS-CoV-2 was frequent in the assessed Colombian indigenous communities, as 38.5% of the study participants showed signs of exposure to SARS-CoV-2, which confirms the need to include these indigenous communities in screening and vaccination programs.

10.
EBioMedicine ; 70: 103524, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1356202

ABSTRACT

BACKGROUND: Patients with chronic renal insufficiency on maintenance haemodialysis face an increased risk of COVID-19 induced mortality and impaired vaccine responses. To date, only a few studies have addressed SARS-CoV-2 vaccine elicited immunity in this immunocompromised population. METHODS: We assessed immunogenicity of the mRNA vaccine BNT162b2 in at-risk dialysis patients and characterised systemic cellular and humoral immune responses in serum and saliva using interferon γ release assay and multiplex-based cytokine and immunoglobulin measurements. We further compared binding capacity and neutralization efficacy of vaccination-induced immunoglobulins against emerging SARS-CoV-2 variants Alpha, Beta, Epsilon and Cluster 5 by ACE2-RBD competition assay. FINDINGS: Patients on maintenance haemodialysis exhibit detectable but variable cellular and humoral immune responses against SARS-CoV-2 and variants of concern after a two-dose regimen of BNT162b2. Although vaccination-induced immunoglobulins were detectable in saliva and plasma, both anti-SARS-CoV-2 IgG and neutralization efficacy was reduced compared to a vaccinated non-dialysed control population. Similarly, T-cell mediated interferon γ release after stimulation with SARS-CoV-2 spike peptides was significantly diminished. INTERPRETATION: Quantifiable humoral and cellular immune responses after BNT162b2 vaccination in individuals on maintenance haemodialysis are encouraging, but urge for longitudinal follow-up to assess longevity of immunity. Diminished virus neutralization and interferon γ responses in the face of emerging variants of concern may favour this at-risk population for re-vaccination using modified vaccines at the earliest opportunity. FUNDING: Initiative and Networking Fund of the Helmholtz Association of German Research Centres, EU Horizon 2020 research and innovation program, State Ministry of Baden-Württemberg for Economic Affairs, Labour and Tourism.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , Vaccines, Synthetic/immunology , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Female , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Renal Dialysis/methods , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Vaccination/methods
11.
Nat Commun ; 12(1): 3109, 2021 05 25.
Article in English | MEDLINE | ID: covidwho-1243298

ABSTRACT

SARS-CoV-2 is evolving with mutations in the receptor binding domain (RBD) being of particular concern. It is important to know how much cross-protection is offered between strains following vaccination or infection. Here, we obtain serum and saliva samples from groups of vaccinated (Pfizer BNT-162b2), infected and uninfected individuals and characterize the antibody response to RBD mutant strains. Vaccinated individuals have a robust humoral response after the second dose and have high IgG antibody titers in the saliva. Antibody responses however show considerable differences in binding to RBD mutants of emerging variants of concern and substantial reduction in RBD binding and neutralization is observed against a patient-isolated South African variant. Taken together our data reinforce the importance of the second dose of Pfizer BNT-162b2 to acquire high levels of neutralizing antibodies and high antibody titers in saliva suggest that vaccinated individuals may have reduced transmission potential. Substantially reduced neutralization for the South African variant further highlights the importance of surveillance strategies to detect new variants and targeting these in future vaccines.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccination , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibody Formation , COVID-19/blood , Female , Gene Expression , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Mutation , Neutralization Tests , Protein Binding , Protein Domains/genetics , Receptors, Coronavirus/metabolism , Recombinant Proteins , SARS-CoV-2/genetics , Saliva/immunology , Saliva/virology
12.
EMBO Rep ; 22(5): e52325, 2021 05 05.
Article in English | MEDLINE | ID: covidwho-1204402

ABSTRACT

In light of the COVID-19 pandemic, there is an ongoing need for diagnostic tools to monitor the immune status of large patient cohorts and the effectiveness of vaccination campaigns. Here, we present 11 unique nanobodies (Nbs) specific for the SARS-CoV-2 spike receptor-binding domain (RBD), of which 8 Nbs potently inhibit the interaction of RBD with angiotensin-converting enzyme 2 (ACE2) as the major viral docking site. Following detailed epitope mapping and structural analysis, we select two inhibitory Nbs, one of which binds an epitope inside and one of which binds an epitope outside the RBD:ACE2 interface. Based on these, we generate a biparatopic nanobody (bipNb) with viral neutralization efficacy in the picomolar range. Using bipNb as a surrogate, we establish a competitive multiplex binding assay ("NeutrobodyPlex") for detailed analysis of the presence and performance of neutralizing RBD-binding antibodies in serum of convalescent or vaccinated patients. We demonstrate that NeutrobodyPlex enables high-throughput screening and detailed analysis of neutralizing immune responses in infected or vaccinated individuals, to monitor immune status or to guide vaccine design.


Subject(s)
COVID-19 , Single-Domain Antibodies , Antibodies, Viral/metabolism , Humans , Immunity , Pandemics , Protein Binding , SARS-CoV-2 , Single-Domain Antibodies/metabolism , Spike Glycoprotein, Coronavirus/metabolism
13.
Nat Commun ; 12(1): 1152, 2021 02 19.
Article in English | MEDLINE | ID: covidwho-1091492

ABSTRACT

The humoral immune response to SARS-CoV-2 is a benchmark for immunity and detailed analysis is required to understand the manifestation and progression of COVID-19, monitor seroconversion within the general population, and support vaccine development. The majority of currently available commercial serological assays only quantify the SARS-CoV-2 antibody response against individual antigens, limiting our understanding of the immune response. To overcome this, we have developed a multiplex immunoassay (MultiCoV-Ab) including spike and nucleocapsid proteins of SARS-CoV-2 and the endemic human coronaviruses. Compared to three broadly used commercial in vitro diagnostic tests, our MultiCoV-Ab achieves a higher sensitivity and specificity when analyzing a well-characterized sample set of SARS-CoV-2 infected and uninfected individuals. We find a high response against endemic coronaviruses in our sample set, but no consistent cross-reactive IgG response patterns against SARS-CoV-2. Here we show a robust, high-content-enabled, antigen-saving multiplex assay suited to both monitoring vaccination studies and facilitating epidemiologic screenings for humoral immunity towards pandemic and endemic coronaviruses.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Serological Testing/methods , COVID-19/immunology , Cross Reactions , Immunity, Humoral , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/immunology , Humans , Immunoassay , Immunoglobulin G/immunology , Phosphoproteins/immunology , SARS-CoV-2/immunology , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/immunology
14.
Nat Immunol ; 22(1): 74-85, 2021 01.
Article in English | MEDLINE | ID: covidwho-1065902

ABSTRACT

T cell immunity is central for the control of viral infections. To characterize T cell immunity, but also for the development of vaccines, identification of exact viral T cell epitopes is fundamental. Here we identify and characterize multiple dominant and subdominant SARS-CoV-2 HLA class I and HLA-DR peptides as potential T cell epitopes in COVID-19 convalescent and unexposed individuals. SARS-CoV-2-specific peptides enabled detection of post-infectious T cell immunity, even in seronegative convalescent individuals. Cross-reactive SARS-CoV-2 peptides revealed pre-existing T cell responses in 81% of unexposed individuals and validated similarity with common cold coronaviruses, providing a functional basis for heterologous immunity in SARS-CoV-2 infection. Diversity of SARS-CoV-2 T cell responses was associated with mild symptoms of COVID-19, providing evidence that immunity requires recognition of multiple epitopes. Together, the proposed SARS-CoV-2 T cell epitopes enable identification of heterologous and post-infectious T cell immunity and facilitate development of diagnostic, preventive and therapeutic measures for COVID-19.


Subject(s)
COVID-19/immunology , Epitopes, T-Lymphocyte/immunology , Peptides/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Viral Vaccines/immunology , COVID-19/prevention & control , COVID-19/virology , Cross Reactions/immunology , HLA-DR Antigens/immunology , HLA-DR Antigens/metabolism , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class I/metabolism , Humans , Immunologic Memory/immunology , SARS-CoV-2/physiology , T-Lymphocytes/metabolism , Viral Vaccines/administration & dosage
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